Rev. Med. Chir. Soc. Med. Nat., Iaşi – 2013 – vol. 117, no. 3
INTERNAL MEDICINE - PEDIATRICS
ORIGINAL PAPERS
HEART RATE PARTICULARITIES IN CHRONIC OBSTRUCTIVE
PULMONARY DISEASE
M. Roca 1, F. Mitu2, Iulia-Cristina Roca 3, T. Mihăescu 4
University of Medicine and Pharmacy "Grigore T. Popa" – Iasi
Faculty of Medicine
1. Ph.D. student
2. Discipline of Medical Semiology
3. Discipline of Emergency Medicine
4. Discipline of Pneumology
HEART RATE PARTICULARITIES IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE (Abstract): Autonomic nervous system dysfunction proved in chronic obstructive
pulmonary disease (COPD) patients might determine an elevated cardiovascular risk by heart
rate alteration. Aim: To assess the particularities of heart rate as a possible cardiovascular
risk factor in COPD patients. Materials and Methods: This prospective, case-control study
comparatively analyzed the pulse rate continuously recorded with a polygraph in 32 COPD
patients and 29 healthy subjects during rest (supine and sitting position) and during subma ximal exercise (6-minute walk test). The relation between pulse rate and respiratory, functional or clinical alterations was analyzed in COPD patients. Results: The mean pulse rate was
significantly higher during rest and exercise in COPD patients compared with the controls.
However, the chronotropic response determined by exercise was similar in COPD and control groups: 55.19 beats/minute and 57.21 beats/minute, respectively (p=0.686). The mean
pulse rate during exercise correlated with hypoxemia (r=-0.354, p=0.47) and with resting
pulse rate (r=0.871, p<0.001 for supine position). Conclusions: COPD associates elevated
pulse rates during both rest and exercise. Hypoxemia and resting pulse rate are determin atives of chronotropic response during submaximal exercise in COPD patients. Keywords:
COPD, RESTING PULSE RATE, CHRONOTROPIC RESPONSE
One of the specific characteristics in
COPD patients is represented by the presence of complex chronic comorbidities (1).
Cardiovascular diseases represent important comorbidities, resulting in 26% of
cause-specific mortality in COPD patients:
16% sudden death, 4% stroke, 3% myocardial infarction, 3% congestive heart failure
(2). COPD associates an increased risk of
developing acute cardiovascular events
such as cardiac arrhythmia, deep vein
thrombosis, pulmonary embolism, myocar-
616
dial infarction, and stroke (3). However,
the complex pathogenic relation between
COPD and cardiovascular diseases is poorly understood, although there is evidence
for the involvement of some common risk
factors, such as smoking.
Patients with COPD have a lower heart rate recovery after exercise than
healthy people. This alteration was proved
as a strong predictor of mortality in COPD
patients (4). Some researchers suggest that
autonomic nervous system dysfunction
Heart rate particularities in chronic obstructive pulmonary disease
demonstrated in COPD patients may alter
the cardiac autonomic modulation and
subsequently the heart rate (5). These alterations might partially explain the increased
cardiovascular risk in COPD patients. Given the pathogenic and prognostic implications of heart rate, our study aimed to assess the particularities of heart rate as a
possible cardiovascular risk factor in
COPD patients.
MATERIAL AND METHODS
To achieve our goal we performed a
prospective, case-control study in which we
compared heart rate in COPD patients and
subjects without lung diseases.
The study included patients admitted to
the Iasi Clinic of Pulmonary Diseases in
the interval April 2011 - September 2012
diagnosed with COPD according to the
criteria in Global Initiative for Chronic
Obstructive Lung Disease (GOLD) guidelines: chronic dyspnea, cough, or sputum
production, and persistent airflow limitation, confirmed by spirometry (a ratio of
forced expiratory volume in 1 second
(FEV1) to forced vital capacity (FVC) of
<0.7 after bronchodilator administration
(6). The control group included subjects
without history of lung diseases and without clinical symptoms compatible with
COPD diagnosis or respiratory dysfunction,
according to the results of pulmonary function tests. COPD patients and controls were
matched for sex and age. Male gender and
age between 45 and 85 years were inclusion criteria for both COPD and control
group. History of heart rhythm disorders
represented an exclusion criterion for both
COPD and control group.
The study protocol included clinical and
anthropometric assessment of the subjects:
body height and weight were measured and
body mass index (BMI) was calculated. The
degree of dyspnea was estimated for COPD
group using the Modified Medical Respiratory Council (MMRC) dyspnea scale (7).
Health impairment in COPD patients was
measured by St George’s Respiratory Questionnaire (SGRQ). This provides three component scores: symptoms, activity and impacts scores, in addition to SGRQ total score
(8). Smoking history was expressed by the
number of pack-years (py). Pulmonary function was assessed by spirometry, including
postbronchodilator FEV1 measuring, to
confirm the diagnosis in COPD group. All
subjects underwent heart rate evaluation at
rest and during exercise (6-minute walk test,
6MWT). Using a polygraph (SOMNOcheck® Effort, Weinmann®, Germany),
pulse rate and oxygen saturation (SpO2)
were continuously recorded as follows: 6
minutes with the patient in supine position,
6 minutes in sitting position and 6 minutes
during exercise (6MWT). The 6-minute
walk test was performed according to the
standards of American Thoracic Society (9).
The study was approved by the Ethics
Committee of Iasi Clinic of Pulmonary
Diseases, and the patients were enrolled
only after they provided appropriate informed consent.
Data analysis was performed using Statistical Package for the Social Sciences
(SPSS v.16.0.). The data were presented as
mean ± standard deviation (SD). The equality of means for quantitative variables of
the control and COPD groups were assessed for significance using the unpaired
Student’s t-test. In case the assumption of
normality was not met, a nonparametric
test was applied (Mann–Whitney U-test).
Analysis of variance (ANOVA) was used
to test the means equality in case of more
than two samples. The Pearson correlation
coefficient or the Spearman rank correlation coefficient was calculated to assess the
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M. Roca et al.
relationships between various clinical and
functional parameters in COPD patients.
All statistical tests were 2-tailed, and p
values < 0.05 were considered significant
for all analyses.
RESULTS
We enrolled a total of 32 patients in the
COPD group and 29 subjects in the control
group. The COPD group had a higher
smoking index and a lower body mass
index than the control group. The 6-minute
walking distance was significantly higher
for the control group (tab. I).
Regarding pulse rate, both case and
control groups shared a similar trend, the
mean values significantly increasing from
supine to sitting position and from sitting
position to exercise during 6MWT
(p<0.001 for both COPD and control
groups). The results demonstrate significantly higher pulse rate mean values in
COPD subjects than in controls, during rest
as well as during exercise: supine position,
sitting position and 6-minute walk test,
respectively (tab. II, fig. 1). However, no
significant differences were found between
study groups in pulse rate increase (mean
pulse rate differences) from supine to sitting position (p=0.479) and from sitting
position to exercise during 6MWT
(p=0.065).
TABLE I
Anthropometric, clinical and respiratory functional characteristics in the study groups
COPD
Control
n=32
n=29
Subjects n
Age yrs
Weight kg
Height cm
BMI kg∙m-2
Smoking py
MMRC
FEV1
FEV1/FVC
6MWT m
Mean ± SD
65.75 ± 8.79
68.09 ± 17.48
168.59 ± 7.27
23.81 ± 5.18
38.64 ± 19.43
2.28 ± 0.95
38.9 ± 13.5
52.6 ± 11.1
281.4 ± 107.5
Min
51.0
45.0
154.0
17.6
10.0
1
Max
85.0
110.0
192.0
38.1
100.0
4
Mean ± SD
61.72 ± 8.51
83.37 ± 15.93
171.17 ± 5.75
28.37 ± 4.79
17.96 ± 20.13
102.5 ± 14.8
80.7 ± 7.3
426 ± 77.4
Min
48.0
58.6
159.0
20.5
0.0
-
Max
80.0
125.0
180.0
43.3
80.0
-
p value
0.068
<0.001
0.133
<0.001
<0.001
<0.001
<0.001
<0.001
TABLE II
Mean pulse rates - comparison between COPD and control groups
Subjects n
Pulse rate
beats∙min -1
Supine
Sitting
6MWT
618
COPD
Control
n=32
n=29
Mean ± SD
78.16 ± 16.61
82.87 ± 17.03
97.07 ± 2.36
Min
52.2
52.7
90.1
Max
111.3
115.4
103.3
Mean ± SD
66.42 ± 8.57
71.49 ± 8.88
90.6 ± 2.39
Min
51.2
53.8
80.0
Max
87.9
92.4
96.9
p value
0.001
0.002
<0.001
Heart rate particularities in chronic obstructive pulmonary disease
Fig. 1. The trend of pulse rate in the study groups
Even if pulse rate increase seems to be
higher in controls than in COPD group as
a result of the transition from rest to exercise (6MWT), the difference was on the
borderline of statistical significance. The
resting pulse rate (mean pulse rate for
supine position) and peak pulse rate (maximum value during 6MWT) were assessed,
the calculated difference between peak
rate and resting rate representing the chronotropic response to exercise. The chronotropic peak moment was determined as the
time of the peak in pulse rate during the 6
minute period of walk test. The chronotropic response and the chronotropic peak
moment did not show significant differences between COPD and control groups
(tab. III).
TABLE III
Chronotropic response – comparison between COPD and control groups
Subjects n
Pulse rate variation
beats∙min -1
Supine to sitting
Sitting to 6MWT
COPD
Control
n=32
n=29
Mean ± SD
4.71 ± 8.49
14.25 ± 8.58
Mean ± SD
5.07 ± 4.6
19.1 ± 11.47
p value
0.479
0.065
Chronotropic response (beats∙min -1)
55.19 ± 30.93
57.21 ± 26.39
0.686
Chronotropic peak moment (sec)
173.9 ± 114.7
181.9 ± 111.3
0.783
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M. Roca et al.
We searched for potential determinatives of pulse rate alterations in COPD
patients, assessing the relation of this parameter with other clinical or functional
parameters (tab. IV). The mean pulse rate
during 6 minute walk test inversely correlated with mean SpO2. In COPD patients,
SpO2 demonstrated an opposite trend than
pulse rate in relation with exercise, significantly decreasing during walk test as compared with rest in supine position
(p=0.019). However, we did not find other
correlations between pulse rate alteration,
either during rest or exercise, and any other
functional or clinical parameter in COPD
patients, including MMRC dyspnea score,
FEV1 and SGRQ scores. Resting pulse rate
seems to determine the pulse rate increase
during exercise, 6MWT mean pulse rate
strongly correlating with mean pulse rates
for both supine and sitting position
(p<0.001).
TABLE IV
Potential determinatives for the pulse rate alteration in COPD group
Supine pulse rate
Supine pulse rate
Sitting pulse rate
6MWT pulse rate
Sitting pulse rate
6MWT pulse rate
6MWT pulse rate
6MWT SpO2
DISCUSSION
COPD associates an important risk of
cardiovascular disease, the factors responsible for this association remaining largely
unknown. Elevated resting heart rate was
proved to be a strong independent risk
factor for cardiovascular diseases in
healthy subjects (10).
Our results have proved a significantly
higher resting heart rate in COPD patients
compared with controls without lung disease, for either supine or sitting position.
Jensen et al. showed that resting heart rate
was associated with cardiovascular mortality
in a study including 16,696 COPD patients.
They also found a strong association of the
resting heart rate with COPD severity assessed as airway obstruction (11). We did
not find any association between resting
heart rate and FEV1 percent of predicted
value (p=0.54), probably because of the
small size of our study group. Furthermore,
Van Gestel et al. found a significant correla-
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Correlation coefficient r
0.871
0.701
0.819
-0.354
p value
<0.001
<0.001
<0.001
0.047
tion between resting heart rate and exercise
capacity assessed by 6MWT distance (12).
Our study did not prove any association
between resting heart rate and health impairment measured by SGRQ in COPD
patients in either symptoms, activity, impacts, or total scores of SGRQ. Dyspnea
score (MMRC) did not correlate with resting
heart rate, too. The higher resting heart rate
might be explain by autonomic nervous
system dysfunction in COPD patients, resulting in alterations of cardiac autonomic
modulation and enhanced sympathetic tone
at rest (5). Hypoxemia seems to be one of
the determinant factors of this dysfunction,
given the effect of oxygen supplementation
which significantly and favorably alters
autonomic modulation in COPD (13). There
are also studies which obtained divergent
results. Chen et al. found that resting autonomic nervous function of COPD patients is
not different from that of normal controls.
The airway obstruction was not related
Heart rate particularities in chronic obstructive pulmonary disease
to the cardiac autonomic nervous function,
but a worse oxygenation status was associated with increased cardiac vagal and decreased cardiac sympathetic activities in
COPD patients (14).
Most of the researches regarding resting
heart rate in COPD have assessed the patients in supine position. However, the
transition from supine to sitting position is
proved to improve hemodynamics, to decrease the respiratory functional residual
capacity and airflow limitation, and to
allow the accessory muscle use in breathing
(15). These functional mechanisms which
explain the orthopnea in COPD as well as
in heart failure may also result in autonomic modulation and consequently in heart
rate modulation. We found a significant
increase in heart rate determined by transition from supine to sitting position in
COPD patients. The heart rate increase in
COPD patients was similar with the heart
rate increase in healthy subjects (4.71
beats/minute and 5.07 beats/minute, respectively). However the mean heart rate for
sitting position was significantly higher in
COPD patients than in the control group
subjects, maintaining the same trend as in
supine position. The exercise represented
by 6MWT determined a similar chronotropic response in COPD group compared
with control group (55.19 beats/minute and
57.21 beats/minute, respectively). However, the mean heart rate during exercise was
significantly higher in COPD patients than
in controls, maintaining the same trend as
at rest. The mean time for chronotropic
peak reaching, within the 6 minute period
was also similar in COPD and control
groups (173.9 seconds and 181.9 seconds,
respectively). Our results on heart rate
assessment during exercise are different
from the results obtained by Inal Ince et al.
They found a peak heart rate and chronotropic index significantly lower in COPD
patients than in healthy subjects (p<0.05).
Other interesting finding in their study was
the relation between chronotropic response,
BMI, and dyspnea score (MMRC), respectively. Weight and body mass index were
significantly higher than in COPD patients
with
normal
chronotropic
response
(p<0.05). MMRC dyspnea score explained
44% of the variance in chronotropic index
(16). We did not find any correlations between chronotropic response and functional
or clinical parameters in COPD patients,
including MMRC dyspnea score, FEV1 and
SGRQ scores. However, we determined the
chronotropic response during a submaximal
exercise test (6MWT), unlike the study by
Inal Ince et al. who used incremental exercise testing, although the COPD group in
their study included only 25 patients.
The results obtained by Bartels et al.
suggest that cardiac autonomic modulation
is altered in patients with COPD during
maximal exercise. Autonomic changes
were not significantly correlated with age,
gender, body mass index, spirometry, lung
volumes, resting gas exchange, or oxygen
saturation during exercise (17). In our
study, oxygen saturation and resting pulse
rate seem to be the only possible determinatives of pulse rate increase during submaximal exercise, strongly correlating with
the mean pulse rate during 6MWT.
CONCLUSIONS
COPD associates elevated pulse rates
during both rest and exercise. Pulse rate
increasing in transition from supine to sitting position and chronotropic response
during exercise are similar in COPD and
healthy subjects. Hypoxemia and resting
pulse rate are determinatives of chrono-
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M. Roca et al.
tropic response during exercise in COPD
patients. Pulse rate alterations do not correlate with airway obstruction, dyspnea, or
health impairment in chronic obstructive
lung disease. Although more data are needed, elevated heart rate associated during
both rest and exercise might result in increased cardiovascular risk in COPD.
ACKNOWLEDGEMENTS
The study was partially supported by
the European Social Found in Romania,
under the responsibility of the Managing
Authority for the Sectorial Operational
Programme for Human Resources Development 2007-2013 (Project POSDRU
/88/1.5/S/58965).
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